Methods and compositions for pigmented hydrogels and contact lenses

ABSTRACT

In general, the disclosure relates to methods and compositions for preparing colorants useful for preparing pigmented hydrogels. The disclosure further relates to pigmented hydrogels comprising the disclosed colorants. In some instances, the colorant is an alcohol extract of an agro-material, such as turmeric, paprika, spinach, and/or pokorny woad or the colorants comprise one or more of: a carotenoid, chlorophyll-a, chlorophyll-b, a curcumoid, or indigorubin. Alternatively, the colorant can be carbon black. The disclosure further relates to contact lenses comprising the disclosed pigmented hydrogels.

CROSS-REFERENCE TO RELATED APPLICATIONS

This disclosure is a continuation application of U.S. Non-ProvisionalApplication entitled METHODS AND COMPOSITIONS FOR PIGMENTED HYDROGELS,”having Ser. No. 16/690,324 filed on Nov. 21, 2019, which claims thebenefit of and priority to U.S. Provisional Application Ser. No.62/770,247, filed on Nov. 21, 2018 the disclosure of which isincorporated herein by reference in its entirety.

BACKGROUND

Excessive exposure to sunlight or artificial lighting can cause manyocular ailments and aggravates age-related ocular diseases. Suchexposure can trigger various complication such as inflammatory response,growth originating from the bulbar conjunctiva, and Uveal melanoma.Current protective eyewear devices in the market including UV blockingand photo-chromatic spectacles can be effective, but provide for a lowlevel of comfort and inconsistent use as well as poor or no protectionand other wavelengths (high intensity visible light (400-500 nm)). Thus,there is a need for developing contact lenses that provide the desiredprotection.

SUMMARY

Embodiments of the present disclosure relate to methods and compositionsfor preparing colorants useful for preparing pigmented hydrogels andcontact lens, where the pigmented hydrogels can include one or morecolorants.

In an embodiment, the present disclosure provides for a method ofpreparing a contact lens comprising a colorant, the method comprising:exposing the contact lens one or more colorants, wherein the colorantsare incorporated with the contact lens, wherein the contact lenscomprises a hydrogel or a silicone-hydrogel, wherein the colorantscomprise (or consists of or consists essentially of) one or more of:turmeric, paprika, spinach, woad, or carbon black, or wherein thecolorants comprise one or more of: a carotenoid, chlorophyll-a,chlorophyll-b, a curcumoid, indigrubin, indigotin, or indirubin; andseparating the contact lens and the colorant (e.g., residual colorantthat is not absorbed). The present disclosure also provides for ahydrogel or a silicone-hydrogel prepared according the method describedabove and others herein. The present disclosure also provides for acontact lens comprising a hydrogel or a silicone-hydrogel preparedaccording the method described above and others herein.

In an embodiment, the present disclosure provides for a method of makingcontact lens comprising: in situ polymerization of a monomer mixturewith one or more colorants to form a hydrogel or a silicone-hydrogel;and forming the pigmented hydrogel contact lens from the hydrogel or thesilicone-hydrogel, wherein the hydrogel or the silicone-hydrogel entrapsthe colorant.

In an embodiment, the present disclosure provides for a hydrogel or asilicone-hydrogel comprising (or consists of or consists essentially of)a one or more colorants, wherein the colorants comprises (or consists ofor consists essentially of) one or more of: turmeric, paprika, spinach,woad, or carbon black, or wherein the colorants comprise one or more of:a carotenoid, chlorophyll-a, chlorophyll-b, a curcumoid, indigrubin,indigotin, or indirubin.

In an embodiment, the present disclosure provides for a contact lenscomprising one or more colorants, wherein the colorants comprises (orconsists of or consists essentially of) one or more of: turmeric,paprika, spinach, woad, or carbon black, or wherein the colorantscomprise (or consists of or consists essentially of) one or more of: acarotenoid, chlorophyll-a, chlorophyll-b, a curcumoid, indigrubin,indigotin, or indirubin. The contact lens can be made of a hydrogel or asilicone-hydrogel, wherein the hydrogel or a silicone-hydrogel entrapsthe colorants within the hydrogel or a silicone-hydrogel or thecolorants are absorbed onto a surface layer of the contact lens. Thecontact lens can further include a hydrophilic ophthalmic drug, vitaminE, or a combination thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present disclosure can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale, emphasis instead being placed upon clearlyillustrating the principles of the present disclosure. Moreover, in thedrawings, like reference numerals designate corresponding partsthroughout the several views.

FIGS. 1A-1D show various potential applications of the disclosed methodsand compositions. FIG. 1A shows a potential application of pigmentedcontact lenses as alternative occlusion patches for treating amblyopiaand correcting refractive errors. FIG. 1B shows a disclosed Class 1 UVblocking turmeric loaded yellow contact lenses capable of screening >95%UVA, UVB, and UVC radiations. FIG. 1C shows disclosed pigmented siliconehydrogels with varying color intensity imparted by tuning concentrationof the extracted pigment offer a viable treatment option for managingmigraines and photophobia. FIG. 1D shows disclosed silicone hydrogelstinted with pigments extracted from woad and paprika offer selectivefiltering of visible light, aiding CVD patients with enhanced colorperception.

FIGS. 2A-2C show disclosed pigmented hydrogels. FIG. 2A shows ap-hydroxyethyl methacrylate gels tinted with the extracted pigments bydirect entrapment of the pigment in swollen hydrogels. Gels were soakedin solutions containing natural pigments extracted by incorporation of0.5 wt. %-33 wt. % of food colorant loading in ethanol. FIG. 2B shows arepresentative figure demonstrating the synthesis of a tinted lens. FIG.2C shows photographic images of tinted silicone hydrogels formulatedusing the same approach.

FIGS. 3A-3D show experimental absorbance spectra and corresponding fitsof turmeric, spinach powder, paprika and woad powder, respectively, inthe silicone hydrogel matrix. FIG. 3E shows molar absorptivities of thefood colorants utilized in FIGS. 3A-3D.

FIGS. 4A-4E show representative data for the relationship betweenpigment concentration in the solution phase (ethanol) and thatpartitioned in the lens phase.

FIGS. 5A-5F show representative data for the disclosed hydrogel lenses.FIG. 5A shows representative transmittance spectra of 200 μm thickturmeric loaded yellow-pigmented p-HEMA hydrogel lens with 17.09 μg-1 mgof turmeric loading/g of dry lens. These gels were synthesized throughdip soaking of pre-polymerized p-HEMA lenses in turmeric/ethanolsolutions. FIG. 5B shows representative transmittance spectra of 200 pmthick turmeric loaded yellow-pigmented p-HEMA hydrogel lens with6.54-18.95 μg of turmeric loading/g of dry lens. A loss of >50%transmittance is observed for loadings >20 μg of turmeric loading/g ofdry lens. FIG. 5BC shows a photographic image of batches of pigmentedHEMA monomer solutions and the corresponding hydrogels synthesized byin-situ free radical polymerization. The lenses were pigmented by directentrapment of food colorant particles during polymerization. FIG. 5Dshows a representative digital photograph of turmeric loaded siliconehydrogel lenses stored in PBS medium for 7 days. A quick ethanol dip wasdone prior PBS storage to remove surface deposits from the lenses. Nosignificant pigment diffusion was observed. FIG. 5E shows representativeabsorbance spectra indicating presence of leached turmeric from a 200 μmthick turmeric powder loaded silicone hydrogel lens stored in PBS mediumfor 7 days. FIG. 5F shows representative data for the effect ofsterilization on loss of pigment from the lens matrix. No significantchanges in transmittance were observed.

FIGS. 6A-6E show representative data pertaining to disclosed hydrogellenses. FIGS. 6A-6D show representative transmittance spectra of 200 μmthick silicone hydrogel lenses loaded with 35.91 μg-1.93 mg of turmericloading/g of dry lens (yellow), 39.54 μg—1.03 mg of spinach powderloading/g of dry lens (green), 16.62 μg-268.07 μg of paprika loading/gof dry lens (orange), and 18.21 μg-209.72 μg of woad loading/ g of drylens (pink). These gels were synthesized through dip soaking ofpre-polymerized silicone lenses in food colorant/ethanol solutions. FIG.6E shows representative transmittance spectra of 200 μm thick spinachpowder loaded green-pigmented silicone hydrogel lens after exposure tosunlight for 7 days. 11.18 μg-125.15 μg of spinach powder/g of dry lenswas the resultant pigment mass in the degraded lenses. An 82.5%degradation of active pigment extracted from spinach powder induces lossof hue in the lenses, which potentially limits its application to lensesfor migraine therapy. FIG. 6F shows representative transmittance spectraof 200 μm thick turmeric/spinach powder loaded silicone hydrogel lensafter exposure to sunlight for 7 days. The resultant pigment massrecorded was 68.73 μg-1.38 mg of spinach powder loading/g of dry lens.In comparison to control spinach powder loaded lenses, a 50% reductionin degradation of active pigment was observed.

FIGS. 7A-7E show representative photographic images of disclosedhydrogel lenses on rabbit cadaver eyes. FIG. 7A shows a representativephotographic image of a control Albino rabbit cadaver eye. FIGS. 7B-7Cshow representative photographic images of silicone scleral lenssynthesized by induction of curvature through lens blister packs. The 22mm scleral lenses were pigmented by soaking control gels in 17.42 wt. %turmeric/ethanol and 8.71 wt. % turmeric/spinach/ethanol solutions.Photograph of control and tinted version of the scleral lens placed onAlbino rabbit cadaver eyes to show lens transparency and compatibility.FIG. 7D shows a representative photographic image of an Air Optix™ NIGHT& DAY™ AQUA lens that has been pigmented contact using the disclosedmethods and compositions. FIG. 7E shows a representative photographicimage of an ACUVUE® TruEye® lens that has been pigmented contact usingthe disclosed methods and compositions.

FIGS. 8A-8F show representative scanning electron micrograph (SEM)images of disclosed hydrogels loaded with disclosed colorants. The SEMimages are of a 200 μm thick silicone hydrogel loaded with turmeric andspinach powder. These tinted lenses were prepared by soaking in 17.42wt. % turmeric/ethanol, spinach powder/ethanol and paprika/ethanolsolutions. FIGS. 8A-8B show a specific cross-section of a turmericloaded silicone lenses imaged at 40000X-120000X indicating low or nopresence of bound particles in the matrix. While imaging a differentcross-sectional region (FIGS. 8C-8D) at 120000× magnification factor, adistinct grain boundary between the non-spherical turmeric pigmentparticle and the hydrogel phase is revealed. Image analysis reveals theaverage ferret diameter of these pigment particles to be 50 nm whichshows promise for drug delivery applications. FIGS. 8E-8F correspond tolenses tinted with spinach and paprika powders indicating non-specificbinding of the phase separated pigment particles in the lens matrix.

Additional advantages of the present disclosure will be set forth inpart in the description which follows, and in part will be obvious fromthe description, or can be learned by practice of the invention. Theadvantages of the present disclosure will be realized and attained bymeans of the elements and combinations particularly pointed out in theappended claims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION

Many modifications and other embodiments disclosed herein will come tomind to one skilled in the art to which the disclosed compositions andmethods pertain having the benefit of the teachings presented in theforegoing descriptions and the associated drawings. Therefore, it is tobe understood that the disclosures are not to be limited to the specificembodiments disclosed and that modifications and other embodiments areintended to be included within the scope of the appended claims. Theskilled artisan will recognize many variants and adaptations of theaspects described herein. These variants and adaptations are intended tobe included in the teachings of this disclosure and to be encompassed bythe claims herein.

Although specific terms are employed herein, they are used in a genericand descriptive sense only and not for purposes of limitation.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosure.

Any recited method can be carried out in the order of events recited orin any other order that is logically possible. That is, unless otherwiseexpressly stated, it is in no way intended that any method or aspect setforth herein be construed as requiring that its steps be performed in aspecific order. Accordingly, where a method claim does not specificallystate in the claims or descriptions that the steps are to be limited toa specific order, it is no way intended that an order be inferred, inany respect. This holds for any possible non-express basis forinterpretation, including matters of logic with respect to arrangementof steps or operational flow, plain meaning derived from grammaticalorganization or punctuation, or the number or type of aspects describedin the specification.

While aspects of the present disclosure can be described and claimed ina particular statutory class, such as the system statutory class, thisis for convenience only and one of skill in the art will understand thateach aspect of the present disclosure can be described and claimed inany statutory class.

It is also to be understood that the terminology used herein is for thepurpose of describing particular aspects only and is not intended to belimiting. Unless defined otherwise, all technical and scientific termsused herein have the same meaning as commonly understood by one ofordinary skill in the art to which the disclosed compositions andmethods belong. It will be further understood that terms, such as thosedefined in commonly used dictionaries, should be interpreted as having ameaning that is consistent with their meaning in the context of thespecification and relevant art and should not be interpreted in anidealized or overly formal sense unless expressly defined herein.

Prior to describing the various aspects of the present disclosure, thefollowing definitions are provided and should be used unless otherwiseindicated. Additional terms may be defined elsewhere in the presentdisclosure.

DEFINITIONS

As used herein, “comprising” is to be interpreted as specifying thepresence of the stated features, integers, steps, or components asreferred to, but does not preclude the presence or addition of one ormore features, integers, steps, or components, or groups thereof.Moreover, each of the terms “by”, “comprising,” “comprises”, “comprisedof,” “including,” “includes,” “included,” “involving,” “involves,”“involved,” and “such as” are used in their open, non-limiting sense andmay be used interchangeably. Further, the term “comprising” is intendedto include examples and aspects encompassed by the terms “consistingessentially of” and “consisting of.” Similarly, the term “consistingessentially of” is intended to include examples encompassed by the term“consisting of”. In regard to use of “consisting essentially of” inregard to colorants, components that do not effect or substantiallyeffect the color to be imparted to the hydrogel or the silicone-hydrogeland/or contact lenses or can be present in an amount that is consideredan impurity for the preparation of hydrogels or the silicone-hydrogel orcontact lenses.

As used in the specification and the appended claims, the singular forms“a,” “an” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a colorant,” or “alens,” including, but not limited to, two or more such pigments,colorants, or lenses, and the like.

It should be noted that ratios, concentrations, amounts, and othernumerical data can be expressed herein in a range format. It will befurther understood that the endpoints of each of the ranges aresignificant both in relation to the other endpoint, and independently ofthe other endpoint. It is also understood that there are a number ofvalues disclosed herein, and that each value is also herein disclosed as“about” that particular value in addition to the value itself. Forexample, if the value “10” is disclosed, then “about 10” is alsodisclosed. Ranges can be expressed herein as from “about” one particularvalue, and/or to “about” another particular value. Similarly, whenvalues are expressed as approximations, by use of the antecedent“about,” it will be understood that the particular value forms a furtheraspect. For example, if the value “about 10” is disclosed, then “10” isalso disclosed.

When a range is expressed, a further aspect includes from the oneparticular value and/or to the other particular value. For example,where the stated range includes one or both of the limits, rangesexcluding either or both of those included limits are also included inthe disclosure, e.g. the phrase “x to y” includes the range from ‘x’ to‘y’ as well as the range greater than ‘x’ and less than ‘y’. The rangecan also be expressed as an upper limit, e.g. ‘about x, y, z, or less’and should be interpreted to include the specific ranges of ‘about x’,‘about y’, and ‘about z’ as well as the ranges of ‘less than x’, lessthan y′, and ‘less than z’. Likewise, the phrase ‘about x, y, z, orgreater’ should be interpreted to include the specific ranges of ‘aboutx’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’,greater than y′, and ‘greater than z’. In addition, the phrase “about‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’to about ‘y’”.

It is to be understood that such a range format is used for convenienceand brevity, and thus, should be interpreted in a flexible manner toinclude not only the numerical values explicitly recited as the limitsof the range, but also to include all the individual numerical values orsub-ranges encompassed within that range as if each numerical value andsub-range is explicitly recited. To illustrate, a numerical range of“about 0.1% to 5%” should be interpreted to include not only theexplicitly recited values of about 0.1% to about 5%, but also includeindividual values (e.g. about 1%, about 2%, about 3%, and about 4%) andthe sub-ranges (e.g. about 0.5% to about 1.1%; about 5% to about 2.4%;about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and otherpossible sub-ranges) within the indicated range.

As used herein, the terms “about,” “approximate,” “at or about,” and“substantially” mean that the amount or value in question can be theexact value or a value that provides equivalent results or effects asrecited in the claims or taught herein. That is, it is understood thatamounts, sizes, formulations, parameters, and other quantities andcharacteristics are not and need not be exact, but may be approximateand/or larger or smaller, as desired, reflecting tolerances, conversionfactors, rounding off, measurement error and the like, and other factorsknown to those of skill in the art such that equivalent results oreffects are obtained. In some circumstances, the value that providesequivalent results or effects cannot be reasonably determined. In suchcases, it is generally understood, as used herein, that “about” and “ator about” mean the nominal value indicated ±10% variation unlessotherwise indicated or inferred. In general, an amount, size,formulation, parameter or other quantity or characteristic is “about,”“approximate,” or “at or about” whether or not expressly stated to besuch. It is understood that where “about,” “approximate,” or “at orabout” is used before a quantitative value, the parameter also includesthe specific quantitative value itself, unless specifically statedotherwise.

As used herein, the term “effective amount” refers to an amount that issufficient to achieve the desired modification of a physical property ofthe composition or material. For example, an “effective amount” of acolorant refers to an amount that is sufficient to achieve the desiredimprovement in the property modulated by the formulation component, e.g.achieving the desired level of blocking of a desired wavelength. Thespecific level in terms of wt % in a composition required as aneffective amount will depend upon a variety of factors including theamount and type of colorant, type of hydrogel or the silicone-hydrogel,level of target blocking of a desired wavelength, and end use of thehydrogel or the silicone-hydrogel made using the composition.

As used herein, the terms “optional” or “optionally” means that thesubsequently described event or circumstance can or cannot occur, andthat the description includes instances where said event or circumstanceoccurs and instances where it does not.

Unless otherwise specified, temperatures referred to herein are based onatmospheric pressure (i.e. one atmosphere).

DISCUSSION

Embodiments of the present disclosure relate to methods and compositionsfor preparing colorants useful for preparing pigmented hydrogels or thesilicone-hydrogels and pigmented contact lenses, where the pigmentedhydrogels or the silicone-hydrogels and pigmented contact lenses caninclude one or more colorants. In some instances, the colorant (e.g.,also referred to as pigment) is an extract of an agro-material, such asturmeric, paprika, spinach, and/or woad (as well as components of eachagro-material that produce the corresponding color), while the colorantcan also be carbon black, independently or in combination with theagro-material colorants.

In general, the method of preparing a pigmented contact lens including acolorant can include exposing a contact lens (e.g., made of a swellablehydrogel or the silicone-hydrogel) to one or more colorants to form thepigmented contact lens. Exposing can include contacting the contact lensand the colorant(s) for a period of time for the colorant to beincorporated with the contact lens. In an aspect, the colorant can beincorporated with the contact lens by being disposed on the surface ofthe contact lens, forming a layer (e.g., colorant layer or polymer layerincluding the colorant) on the contact lens, absorbed into the surfacelayer of the contact lens, and the like. In an aspect, absorption can beaccomplished by swelling the contact lens material so the molecules ofthe colorant can be absorbed (e.g., infiltrate into) into the surfacelayer of the contact lens. The absorption of the colorant into thesurface layer can include infiltrating of the colorant molecules a shortdistance into the contact lens material (e.g., into gaps or voids withinthe hydrogel or the silicone-hydrogel), where the distance depends uponthe material of the contact lens, the organic liquid, the colorant, andconditions (e.g., time and temperature). For example, the distance canbe about 1 to 35% of the thickness of the contact lens, about 1 to 25%of the thickness of the contact lens, about 1 to 20% of the thickness ofthe contact lens, about 1 to 15% of the thickness of the contact lens,about 1 to 10% of the thickness of the contact lens, or about 1 to 5% ofthe thickness of the contact lens.

In an aspect, the mixing can be done under conditions (e.g., time andtemperature) so that the colorant incorporated with the contact lensreaching an equilibrium (e.g., with the contact lens and the colorant).In an example, mixing can include equilibrating the contact lens (e.g.,made of a hydrogel or silicone-hydrogel) in an organic liquid (e.g.,ethanol, methanol, isopropyl alcohol, dichloromethane, chloroform, ethylacetate, diethyl ether, and combinations thereof) colorant solution, forexample. The organic liquid solution can cause the hydrogel or thesilicone-hydrogel to swell so the colorants can infiltrate into thehydrogel or the silicone-hydrogel. For example, the contact lens can bemade of 2-hydroxyethyl methacrylate (HEMA) or silicone based material aswell as other polymer contact lens material that is described herein andotherwise available. The mixing or equilibrating can include soaking thecontact lens in the solution for about 2 to 16 hours, about 10 to 14hours, or about 12 hours at about room temperature (about 25° C.). Whenreference is made to “hydrogel” this also can include reference to“silicone-hydrogel” as well based on the context upon which it is used.As a result, the term hydrogel may be used as opposed to hydrogel orsilicon-hydrogel.

After the desired amount of colorant is incorporated with the contactlens, the contact lens and the remaining colorant is solution can beseparated. The contact lens can be washed and stored for later use.

Alternatively, the contact lens can be formed by the in situpolymerization of a monomer mixture with the colorant solution includingone or more colorants (e.g., in an organic liquid (e.g., ethanol,methanol, isopropyl alcohol, dichloromethane, chloroform, ethyl acetate,diethyl ether, and combinations thereof)) to form a contact lens havinga pigmented hydrogel that entraps the colorant. The monomer mixture caninclude hydrophilic monomers such as hydroxyethyl methacrylate (HEMA),dimethyl acrylate (DMA), methacrylic acid, or silicone monomer such as3-[tris (trimethylsiloxy)silyl]propyl methacrylate (Tris methacrylate),or polydimethyl siloxane (PDMS), or preferably mixtures of silicone andhydrophilic monomers, as well as those those described herein.Additionally, additives such as polyvinyl alcohol, polyvinylpyrrolidone, hyaluronic acid, crosslinker EGDMA—ethylene glycoldimethacrylate, PDMS—poly dimethyl siloxane can be added to theformulation. Hydrogels or silicone-hydrogels formed from these monomerare also included within the types of hydrogel or silicone-hydrogelsthat the contact lens can be made of. When reference is made to“hydrogel” this also can include reference to “silicone-hydrogel” aswell based on the context upon which it is used.

In an alternative approach, mixing or the in situ polymerization can beaccomplished by incorporating these colorant by incorporating colorantsinto nanoparticles (e.g., micro-emulsions, liposomes, polymericnanoparticles, and the like about 10 to 500 nm or about 10 to 200 nm indiameter) and using them in the methods described above and herein.

In an aspect, the colorant can be included in an organic liquid solution(e.g., ethanol solution). For example, the ethanol solution can includeone or more colorants (e.g., turmeric, paprika, spinach, woad, and/orcarbon black). In an aspect, the colorant can be an organic liquid(e.g., ethanol, methanol, isopropyl alcohol, dichloromethane,chloroform, ethyl acetate, diethyl ether) extract of turmeric, paprika,spinach, woad, or combinations thereof. The organic liquid (e.g.,ethanol, methanol, isopropyl alcohol, dichloromethane, chloroform, ethylacetate, diethyl ether) extract of turmeric can include about 0.006 wt.%-5 wt. % of colorant or about 0.006 wt. %-3.25 wt. % of colorant. Theorganic liquid (e.g., ethanol, methanol, isopropyl alcohol,dichloromethane, chloroform, ethyl acetate, diethyl ether) extract ofpaprika can include about 0.001 wt. %-6 wt. % of colorant or about 0.054wt. %-4.81 wt. % of colorant. The organic liquid (e.g., ethanol,methanol, isopropyl alcohol, dichloromethane, chloroform, ethyl acetate,diethyl ether) extract of spinach can include about 0.001 wt. %-6 wt. %of colorant or about 0.064 wt. %-4.45 wt. % of colorant. The organicliquid (e.g., ethanol, methanol, isopropyl alcohol, dichloromethane,chloroform, ethyl acetate, diethyl ether) extract of paprika can includeabout 0.001 wt. %-0.5 wt. % of colorant or about 0.002 wt. %-0.022 wt. %of colorant.

In an alternative approach the components in turmeric, paprika, spinach,and/or woad that provide the color or act as the colorant can be usedinstead or in combination with the turmeric, paprika, spinach, and/orwoad. The chemical components can include carotenoids (e.g., carotene,xanthophylls, xanthophyll esters), chlorophyll-a and/or -b, curcumoids(e.g., curcumin, dimethoxy curcumin, bisdemethoxy curcumin), indigrubin,indigotin, and/or indirubin. The amounts of each of these componentswould correspond to the amount of these chemicals that are provided bythe amounts of turmeric, paprika, spinach, and/or woad as describedabove. The amounts of each of these components in the hydrogel orcontact lens would correspond to the amount of these chemicals that areprovided by the amounts of turmeric, paprika, spinach, and/or woad asdescribed herein for the hydrogel or contact lens. The components can beused in an organic liquid solution, in in situ polymerization, innanoparticles, and the like to form the contact lens.

In regard to carbon black, the carbon black can be incorporated directlyadding it at about 0.01 to 1 wt. % or about 0.3 wt. % in the monomerformulation. Alternatively, carbon black can be put in solution (e.g., asolvent such as water, ethanol, methanol, isopropyl alcohol,dichloromethane, chloroform, ethyl acetate, diethyl ether) where thesolution can include about 0.01 to 5 wt. % of the carbon black or about0.01 to 1 wt. % of carbon black.

After the contact lens and the colorant are mixed (e.g., equilibrated)the contact lens (also referred to as the “pigmented contact lens”) andthe colorant can be separated. For example, the organic liquid used inloading the colorant can be extracted by drying or soaking the lens in asuitable buffer. After extraction, the contact lens can be rapidlyrinsed with the organic liquid (e.g., ethanol) to remove the surfacedeposits. In addition or alternatively, the pigmented contact lens canbe rinsed with in an isotonic aqueous solution (e.g., phosphate-bufferedsaline (PBS)). In addition, the lens can be packaged in a buffer orartificial tears.

In general, the method provided herein can be used to produce apigmented hydrogel, which can be used to form a contact lens. In otherembodiments, the pigmented hydrogel can be used in other articles otherthan the contact lens. Discussion herein regarding the contact lens canbe applied to other articles as is appropriate. The pigmented hydrogel(e.g., the contact lens or other article) can include one or morecolorants, where the colorant comprises one or more of: turmeric,paprika, spinach, woad, or carbon black and/or carotenoids (e.g.,carotene, xanthophylls, xanthophyll esters), chlorophyll-a and/or -b,curcumoids (e.g., curcumin, dimethoxy curcumin, bisdemethoxy curcumin),indigrubin, indigotin, and/or indirubin.

In an aspect, the amount of colorant (e.g., turmeric, paprika, spinach,woad, and carbon black) present in the contact lens or hydrogel can varydepending upon the desired results. In general, the amount of turmericin the contact lens or hydrogel can be about 2 mg/g contact lens orhydrogel to 700 micrograms/g contact lens or hydrogel or about 30micrograms/g contact lens or hydrogel to 700 micrograms/g contact lensor hydrogel. In general, the amount of spinach in the contact lens orhydrogel can be about 30 mg/g hydrogel to 600 micrograms/g contact lensor hydrogel or about 90 micrograms/g contact lens or hydrogel to 600micrograms/g contact lens or hydrogel. In general, the amount of paprikain the contact lens or hydrogel can be about 15 micrograms/g contactlens or hydrogel to 300 micrograms/g contact lens or hydrogel or about50 micrograms/g contact lens or hydrogel to 300 micrograms/g contactlens or hydrogel. In general, the amount of woad in the contact lens orhydrogel can be about 15 micrograms/g contact lens or hydrogel to 80micrograms/g contact lens or hydrogel or about 20 micrograms/g contactlens or hydrogel to 80 micrograms/g contact lens or hydrogel. The amountof carotenoids (e.g., carotene, xanthophylls, xanthophyll esters),chlorophyll-a and/or -b, curcumoids (e.g., curcumin, dimethoxy curcumin,bisdemethoxy curcumin), indigrubin, indigotin, and/or indirubin presentbased on these amounts could also be used by directly including one ormore of these compounds as opposed to or in combination with theagro-material itself.

The colorants disclosed herein can be surface active, i.e., manycompounds including ophthalmic drugs can bind to the surface of theparticles and or molecules, resulting in an increase in drug loadingand/or release duration. The hydrophobic ophthalmic drugs such ascyclosporine, dexamethasone, latanoprost, bimatoprost can be co-loadedwith the colorants by adding the drugs to the solution of colorants inorganic liquids. Vitamin E that is used as a diffusion barrier can alsobe added to the mixture to result in loading of the colorants forselective light blocking, vitamin E for controlled release of the drug,and the drug for treatment of ophthalmic diseases. The typical vitamin Eloading desired ranges from 5% to 40% (w/w) in the dried contact lens.Hydrophilic drugs such as timolol, dorzolamide, brimonidine, cysteaminecan be loaded sequentially, i.e., soaking the lens already loaded withcolorant or colorant and vitamin E into the drug solution for a 1 hr to7 days depending on the time needed for equilibration. The mass of drugsvary depending on the disease and the duration of release, but onaverage amounts range from 100 to 500 microgram. The presence of thecolorant could also help in reducing the degradation rate of drugs thatare prone to degradation.

COMPOSITIONS AND METHODS

The American conference of governmental industrial hygienists (ACGIH)recommends a threshold UV-A (spectral range of 315 nm-400 nm) ocularexposure limit of less than 1 MW/cm² for periods greater than 1000seconds (Refs. 1-3). Excessive exposure to sunlight or artificiallighting can cause many ocular ailments and aggravates age-relatedocular diseases. UV exposure can trigger serious complications such asinflammatory response to the corneal endometrium (photo keratitis),growth originating from the bulbar conjunctiva (Pingueculae andptergygia), and Uveal melanoma, a malignant tumor originating from theiris (Refs. 3-5). In adults, IOL blocks UV light, but its ability tocompletely phase out the high energy visible (HEV) radiations is likelylimited (Ref. 6). The development of IOL occurs until a young age of 20,and so UV exposure can potentially hinder the vision of young children(Refs. 7-9). Modern day kids with access to electronic devices includinglaptops and tablets are particularly vulnerable to induced visualstresses upon prolonged viewing and exposure to harmful high energyvisible (HEV) radiation emitted from these devices. Though, the currentprotective eyewear devices in the market including UV blocking andphoto-chromatic spectacles have proven effective, low comfort andinconsistent wear time permit possibility of minor UV exposure (Refs. 4,10, and 11). Additionally, violet (400-440 nm) and blue (440-500 nm)which comprise the shorter wavelength and thus high energy part of thevisible spectrum could also cause retinal damage particularly becausethese components of the spectrum are not blocked by the cornea or theintra ocular lens (Ref. 12). Thus, there is a need for developingcontact lenses that block UV as well as high intensity visible light(400-500 nm).

Another potential application of the tinted contacts includes treatingphotophobia and refractive errors in amblyopic children. Photophobia isan eye disorder associated with the patient's abnormal sensitivity oflight preventing visual acuity during daylight (Refs. 13-18). It alsoimpairs visual functioning in an illuminated indoor setting. Amblyopiais a medical condition which involves poor visual acuity due to immaturevisual centers in the brain responsible for visual processing (Refs. 9and 19-24). With a prevalence of approximately 2% of the US population,it is one of the common causes of decreased visual acuity in newborns,infants and toddlers. The processing of physical objects by visualcenters in the brain through high-resolution images captured by theretina is critical for visual development in infants. An orthodoxtreatment for amblyopia in children involves occluding or patching theunaffected eye to improve acuity of the affected eye (Refs. 20-23).Since an amblyopic eye is misaligned with its neighbor, it isaccompanied by refractive errors and generates dissimilar retinalimages, which impairs visual development in children. A pigmentedcontact lens with a darker hue can also be used as alternative occlusionpatches to treat amblyopic population, thereby reducing wear discomfortdue to patching for a prolonged duration. Another more recent treatmentfor amblyopia is based on putting on a red colored lens on one eye and agreen colored lens on the other, forcing both eyes to be functional asthe child views red and green images. Thus, placing a red tinted contacton one eye and a green tinted lens on the other could be an effectivefor treating amblyopia. Innovative binocular iPad treatment and contactlens treatment have also been proposed for management of anisometropicamblyopia (Refs. 24-25).

Another indication that can potentially benefit from tinted contacts iscolor vision deficiency. About 8-10% of the current color-blindpopulation, especially 8% of the males and 0.5% of females havedichromatic vision (Refs. 26-27).The dichromatic population areclassified as red-green color deficient and blue-yellow color deficient.The two common subgroups of red-green color deficiency includedeuteranopia and protanopia. Corrective glasses coated with multiplelayers to block a selective bandwidth from the visible spectrum(˜540-570 nm, an overlap between the red and green color regimes) isrecommended to enhance color perception among CVD population. Though,optical assistive devices like Enchroma glasses are promising foreffective CVD management, their high cost and issues with weardiscomfort are still issues to be addressed (Ref. 28). Tritanopia orblue-yellow color blindness is a rarer form of color-blindness occurringin ˜1% of the male and 0.03% of the female population (Ref. 26). Contactlenses which can selectively filter portions of cyan and green light(˜450-510 nm) can help CVD patients to discriminate between blue andyellow hues of the objects that are visually processed. To achieveblocking of selected wavelength range of light, the lens matrix couldpotentially be tinted to transform it to a multi notch filter.

The extractable pigments that govern the color of natural food powdersperceived could aid in this transfiguration (Refs. 29-68). Beyondflavoring and dyeing, the agro-food powders including tumeric, paprika,spinach and woad powders are commonly considered as nutraceuticals(Refs. 36-38). Studies in the past decade have shown pigments extractedfrom these powders to possess multiple health benefits (Refs. 29, 30,33, 35, 38, 39, 51, and 63). These include anticancer, antibacterialproperties, improved brain function (BDNF booster), effective rheumatoidarthritis and blood pressure management (Refs. 29, 39, and 51). A widearray of these medicinal benefits has encouraged development ofefficient and novel extraction methods in the past decade. These methodscommonly involve steam distillation of plant products or food powders,extraction by dissolution in organic solvents and supercritical carbondi-oxide (Refs. 30, 34, 40, 41, 43-47, 50-55, 57-63, and 65). Further,improved HPLC and NMR characterization have enabled accurate pigmentdetection and structural identification (Refs. 31, 32, 42-44, 46, 48,49, 52-56, and 66-68). These hue imparting pigments include (see Refs.29, 32, 35, 44, 60, and 63): curcumoids (turmeric), carotenoids(paprika), chlorophyll (spinach), and indigotan/indirubin (woad powder).The potential benefits associated with these pigments for oculartherapeutics have still not been extensively explored.

The present disclosure pertains to methods and compositions forfabrication of a tinted contact lens that blocks UV, as well as selectedportions of the visible light to address the indications discussedabove. The approach is based on loading colored pigments extracted fromnatural agro-products. Without wishing to be bound by a particulartheory, it is believed that the agro-origin of the powders can lead toimproved lens biocompatibility. Moreover, the use of ethanol as a mediumfor extraction can improve the tendency of an extracted pigment toremain entrapped in the lenses during storage. The entrapped pigmentsare significantly larger than the pore size in the lenses and should notinduce wear scattering of the visible light, thereby retaining clarity.Based on the specific indications targeted, in the examples hereinbelow, various extracted pigments were specifically examined: use ofturmeric for blocking high intensity visible light; spinach and paprikafor developing green and red tints; and woad for developing lenses forCVD patients. FIGS. 1A-1D illustrate the various indications that couldbenefit from the methods and compositions for tinted contacts in thepresent disclosure.

REFERENCES

References are cited herein throughout using the format of referencenumber(s) enclosed by parentheses corresponding to one or more of thefollowing numbered references. For example, citation of referencesnumbers 1 and 2 immediately herein below would be indicated in thedisclosure as (Refs. 1 and 2).

-   Ref. 1. S. Gause, A. Chauhan, J. Mater. Chem. B, 2016, 4, 327.

-   Ref. 2. D. G. Pitts, A. P. Cullen, P. D. Hacker, Invest. Ophthalmol.    Vis. Sci. 1977, 16, 932.

-   Ref. 3. J. E. Roberts, J. Photochem. Photobiol. B, 2001, 64, 136.

-   

Ref. 4. D. H. Sliney, J. Photochem. Photobiol. B, 2001, 64, 166.

-   Ref. 5. J. A. Zuclich, J. S. Connolly, Invest. Ophthalmol. Vis. Sci.    1976, 15, 760.-   Ref. 6. E. Lai, B. Levine, J. Ciralsky, Curr. Opin. Ophthalmol.    2014, 25, 35.-   Ref. 7. G. E. Quinn, J. A. Berlin, T. L. Young, S. Ziylan, R. A.    Stone, Ophthalmology, 1995, 102, 180.-   Ref. 8. M. Scheiman, M. Gallaway, R. Coulter, F. Reinstein, E.    Ciner, C. Herzberg, M. Parisi, J. Am. Optom. Assoc. 1996, 67, 193.-   Ref. 9. K. W. Wright, Visual Development and Amblyopia, in Pediatric    Ophthalmology and Strabismus, 157, Springer, N,Y., USA 2003.-   Ref. 10. E. Feretis, P. Theodorakopoulos, C. Varotsos, M.    Efstathiou, C. Tzanis, T. Xirou, N. Alexandridou, M. Aggelou,    Environmental Science and Pollution Research, 2002, 9 163.-   Ref. 11. M. Lira, E. M. Dos Santos Castanheira, Optom. Vis. Sci.    2009, 86, 332.-   Ref. 12. M. A. Mainster, Br. J. Ophthalmol. 2006, 90, 784.-   Ref. 13. K. B. Digre, K. C. Brennan, J. Neuro-ophthalmol. 2012, 32,    68.-   Ref. 14. M. I. Kaiser-Kupfer, R. C. Caruso, D. S. Minkler, W. A.    Gaahl, Arch. Ophthalmol. 1986, 104, 706.-   Ref. 15. A. Main, A. Dowson, M. Gross, Headache. 1997, 37,492.-   Ref. 16. S. D. Silberstein, J. J. Armellino, H. D. Hoffman, J. P.    Battikha, S. W. Hamelsky, W. F. Stewart, R. B. Lipton, Clin. Ther.    1999, 21, 475.-   Ref. 17. S. D. Silberstein, N. Mathew, J. Saper, S. Jenkins,    Headache. 2000, 40, 445.-   Ref. 18. P. Volker, O. Wolfgang, H. Wolfgang, Cephalalgia. 1990, 10,    77.-   Ref. 19. A. L. Webber, J. Wood, Clin. Exp. Optom. 2005, 88, 365.-   Ref. 20. R. S. Collins, M. E. McChesney, C. A. McCluer, M. P.    Schatz, J. AAPOS, 2008, 12, 565.-   Ref. 21. J. J. Dutton, Surv. Ophthalmol. 1990, 34, 365.-   Ref. 22. S. E. Loudon, H. J. Simonsz, Strabismus. 2005, 13, 93.-   Ref. 23. B. J. Kushner, Arch. Ophthalmol. 2002, 120, 387.-   Ref. 24. C. J. Roberts, G. G. Adams, Eye (Lond). 2002, 16, 577.-   Ref. 25. E. E. Birch, S. L. Li, R. M. Jost, S. E. Morale, A. De La    Cruz, D. Stager Jr. L. Dao, D. R. Stager Sr. J. AAPOS. 2015, 19, 6.-   Ref. 26. A. R. Badawy, M. U. Hassan, M. Elsherif, Z. Ahmed, A. K.    Yetisen, H. Butt, Adv. Healthcare Mater. 2018, 7, 1800152.-   Ref. 27. J. D. Mollon, J. Pokomy, and K. Knoblauch, Normal and    Defective Colour Vision, Oxford University Press, 2003.-   Ref. 28. N. Almutairi, J. Kundart, N. Muthuramalingam, J. Hayes, K.    Citek, Assessment of Enchroma Filter for Correcting Color Vision    Deficiency, 2017.-   Ref. 29. V. S. Govindarajan, W. H. Stahl, CRC Critical Reviews in    Food Science and Nutrition, 1980, 12, 199.-   Ref. 30. M. H. Abdeldaiem, American Journal of Food Science and    Technology, 2014, 2, 36.-   Ref. 31. K. Inoue, Y. Yoshimura, H. Nakazawa, Analytical Letters,    2001, 34, 1711.-   Ref. 32. G. K. Jayaprakasha, L. Jagan Mohan Rao, K. K. Sakariah, J.    Agric. Food Chem. 2002, 50, 3668.-   Ref. 33. R. Kuttan, P. C. Sudheeran, C. D. Josph, Tumori. 1987, 73,    29.-   Ref. 34. A. C. C. M. Manzan, F. S. Toniolo, E. Bredow, N. P.    Povh, J. Agric. Food Chem. 2003, 51, 6802.-   Ref. 35. K. Priyadarsini, Molecules, 2014, 19, 20091.-   Ref. 36. S. Saxena, A. S. M. Raja, S. S. Muthu, Natural Dyes:    Sources, Chemistry, Application and Sustainability Issues, in    Roadmap to Sustainable Textiles and Clothing: Eco-friendly Raw    Materials, Technologies, and Processing Methods, 37, Springer,    Singapore, 2014.-   Ref. 37. R. Siva, Current Science, 2007, 92, 916.-   Ref. 38. K. Srinivasan, J. Food Reviews Inter. 2005, 21, 167.-   Ref. 39. I. Chattopadhyay, K. Biwas, U. Bandyopadhyay, R. K.    Banerjee, Current Science, 2004, 87,44.-   Ref. 40. G. A. Csiktusnadi Kiss, E. Forgacs, T. Cserhati, T.    Mota, H. Morais, A. Ramos, J. Chromatogr. A. 2000, 889, 41.-   Ref. 41. A. Ambrogi, D. A. Cardarelli, R. Eggers, J. Food Sci. 2002,    67, 3236.

Ref. 42. P. Bhosale, I. V. Ermakov, M. R. Ermakov, W. Gellermann, P. S.Bernstein, J. Agric. Food Chem. 2004, 52,3281.

-   Ref. 43. P. A. Biacs, B. Czinkotai, A. Hoschke, J. Agric. Food Chem.    1992, 40, 363.-   Ref. 44. P. A. Biacs, H. G. Daood, A. Pavisa, F. Hajdu, J. Agric.    Food Chem. 1989, 37, 350.

Ref. 45. H. G. Daood, V. Illes, M. H. Gnayfeed, B. Meszaros, G. Horvath,J. Supercrit. Fluids. 2002, 23, 143.

-   Ref. 46. C. Fisher, J. A. Kocis, J. Agric. Food Chem. 1987, 35, 55.-   Ref. 47. M. H. Gnayfeed, H. G. Daood, V. Illes, P. A. Biacs J.    Agric. Food Chem. 2001, 49, 2761.-   Ref. 48. D. Hornero-Méndez, M. I. Minguez-Mosquera, J. Agric. Food    Chem. 2001, 49, 3584.-   Ref. 49. Y. Ittah, J. Kanner, R. Granit, J. Agric. Food Chem. 1993,    41, 899.-   Ref. 50. M. Jarén-Galán, U. Nienaber, S. J. Schwartz, J. Agric. Food    Chem. 1999, 47,3558.-   Ref. 51. A. Levy, S. Harel, D. Palevitch, B. Akiri, E. Menagem, J.    Kanner, J. Agric. Food Chem. 1995, 43, 362.-   Ref. 52. M. I. Minguez-Mosquera, D. Hornero-Mendez, J. Agric. Food    Chem. 1993, 41, 1616.-   Ref. 53. M. I. Minguez-Mosquera, D. Hornero-Mendez, J. Agric. Food    Chem. 1994, 42, 1555.-   Ref. 54. M. I. Minguez-Mosquera, A. Perez-Galvez, J. Agric. Food    Chem. 1998, 46, 5124.-   Ref. 55. V. Pasquet, J. R. Cherouvrier, F. Farhat, V. Thiery, J. M.    Piot, J. B. Berard, R. Kaas, B. Serive, T. Patrice, J. P.    Cadoret, L. Picot, Process Biochemistry, 2011, 46, 59.-   Ref. 56. A. Gauthier-Jaques, K. Bortlik, J. Hau, L. B. Fay, J.    Agric. Food Chem. 2001, 49, 1117.-   Ref. 57. K. Iriyama, N. Ogura, A. Takamiya, J. Biochem. 1974, 76,    901.-   Ref. 58. K. Iriyama, M. Shiraki, M. Yoshiura, J. Liquid Chromatogr.    1979, 2, 255.-   Ref. 59. R. Moran, Plant Physiology, 1982, 69, 1376.-   Ref. 60. H. T. Quach, R. L. Steeper, G. W. Griffin, J. Chem. Edu.    2004, 81, 385.-   Ref. 61. E. L. Smith, Science. 1938, 88, 170.-   Ref. 62. N. Yamauchi, A. E. Watada, J. Am. Soc. Hortic. Sci. 1991,    116, 58.-   Ref. 63. P. Aobchey, S. Phutrakul, S. Sinchaikul, S. T. Chen, CM. J.    Sci. 2007, 34, 329.-   Ref. 64. G. Carr, Oxford J. Arch. 2005, 24, 273.-   Ref. 65. N. Chanayath, S. Lhieochaiphant, S. Phutrakul, CMU J. 2002,    1,149.-   Ref. 66. W. Laitonjam, W. Sujata, Intr. J. Plant Physiology Biochem.    2011, 3, 108.-   Ref. 67. T. Maugard, E. Enaud, P. Choisy, M. D. Legoy,    Phytochemistry. 2001, 58, 897.-   Ref. 68. P. Vandenabeele, L. Moens, Analyst. 2003, 128, 187.-   Ref. 69. M. K. Blackburn, R. D. Lamb, K. B. Digre, A. G.    Smith, J. E. A. Warner, R. W. McClane, S. D. Nandedkar, W. J.    Lansgeberg, R. Holubkov, B. J. Katz, Ophthalmology. 2009, 116, 997.-   Ref. 70. R. Noseda, V. Kainz, M. Jakubowski, J. J. Gooley, C. B.    Saper, K. Digre, R. Burstein, Nat Neurosci, 2010, 13, 239.-   Ref. 71. A. J. Wilkins, I. Nimmo-Smith, A. I. Slater, L. Bedocs,    Lighting Res. Technol. 1989, 21,-   Ref. 72. H. J. Jung, M. A. Jaoude, B. E. Carbia, C. Plummer, A.    Chauhan, J. Control. Release. 2013, 165, 82.-   Ref. 73. J. Kim, A. Conway, A. Chauhan, Biomaterials, 2008, 29,    2259.-   Ref. 74. J. Kim, C. C. Peng, A. Chauhan, J. Control. Release, 2010,    148, 110.-   Ref. 75. C. C. Peng, A. Chauhan, J. Control. Release, 2011, 154,    267.-   Ref. 76. H. V. Nong, L. X. Hung, P. N. Thang, V. D. Chinh, L. V. Vu,    P.T. Dung, T. V. Trung, P. T. Nga, SpringerPlus. 2016, 5, 1174.-   Ref. 77. S. Aronoff, Chem. Rev. 1950, 47, 175.-   Ref. 78. O. M. Marana, T. J. B Garcia, T. G. Diaz, Analytical    Letters, 2016, 49, 1184.-   Ref. 79. W. R. Brode, E. G. Pearson, G. M. Wyman, J. Am. Chem. Soc.    1954, 76, 1034.-   Ref. 80. D. Hornero-Mendez, M. I. Minguez-Mosquera, J. Agric. Food    Chem. 2001, 49, 3584.

Now having described the aspects of the present disclosure, in general,the following Examples describe some additional aspects of the presentdisclosure. While aspects of the present disclosure are described inconnection with the following examples and the corresponding text andfigures, there is no intent to limit aspects of the present disclosureto this description. On the contrary, the intent is to cover allalternatives, modifications, and equivalents included within the spiritand scope of the present disclosure.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how thecompounds, compositions, articles, devices and/or methods claimed hereinare made and evaluated, and are intended to be purely exemplary of thedisclosure and are not intended to limit the scope of what the inventorsregard as their disclosure. Efforts have been made to ensure accuracywith respect to numbers (e.g. amounts, temperature, etc.), but someerrors and deviations should be accounted for. Unless indicatedotherwise, parts are parts by weight, temperature is in ° C. or is atambient temperature, and pressure is at or near atmospheric.

2. Experimental Section 2.1 Materials

The primary constituents of the hydrogels including 2-hydroxyethylmethacrylate (HEMA, 97%) monomer, ethylene glycol dimethyl acrylate(EGDMA), 1-Vinyl-2-pyrrolidinone (NVP), and Dimethyl acrylamide (DMA)were purchased from Sigma-Aldrich.3-Methacryloxy-propyl-tris-(Trimethyl-siloxy) silane and TRIS monomerwere obtained from Silar (Wilmington, N.C., USA). Ocular medicationsincluding timolol maleate (≥98%) and dexamethasone (≥98%) were purchasedfrom Sigma-Aldrich Chemicals (St. Louis, Mo., USA). The macromerAcryloxy Terminated Ethylene-oxide Dimethyl-siloxane-Ethylene oxide AbaBlock Copolymer (Product Code: DBE-U12) was purchased from Gelest Inc.The UV photo initiator Darocur® TPO was supplied by Ciba SpecialtyChemicals (Tarrytown, N.Y., USA). Vitamin E (DL-alpha tocopherol, >96%)was purchased from Sigma-Aldrich. The food colorants and vegetablepowder samples used for the study including turmeric (UPC:011433071123), spinach powder (UPC: 850627005410 885710046216), paprika(UPC: 852664345023) and woad powder were received from Deep foods(Union, N.J.), Hoosier Hill Farm (Fort Wayne, Ind.),Trader Joe's(Gainesville, Fla.), and Pure Suds (Clark Summits, Pa.). Phosphatebuffered saline (PBS), without calcium and magnesium was purchased fromMedia-tech, Inc. (Manassas, Va., USA). The Albino rabbit cadaver eyesused for the demonstration of tinted lens wear were purchased fromPel-freez biologics (CA, USA). Ethanol (200 proof) was purchased fromDecon Laboratories Inc. (King of Prussia, Pa., USA). All chemicals wereused as received without further purification.

2.2 Synthesis of Silicone and p-HEMA Hydrogels

The p-HEMA hydrogels were synthesized by free radical solutionpolymerization of the monomer through UV photo-initiation (Refs. 72-75).The monomer mixture was prepared by addition of HEMA (2.7 mL), the crosslinker EGDMA (10 μL), and deionized (DI) water (2 mL) in a scintillatingvial. The batch of stirred solution (4.7 mL) was then purged withcompressed nitrogen for 20 minutes to reduce dissolved oxygen, apotential free-radical scavenger. The photo-initiator, Darocur® TPO (6mg) was added to the monomer mixture and subjected to stirring at 300rpm for 10 minutes to ensure complete dissolution of the initiator. Thesolution was then introduced into a mold comprising of two glass platesseparated by a 200 μm polyester spacer. The mold was then placed on anUltraviolet transilluminator UVB-10 (Ultra-Lum, Inc.) and cured byirradiating UVB light (305 nm) for 40 minutes. After polymerization,each gel was removed from the glass mold and was cut into circular gelsof 18 mm diameter was rinsed and stored in PBS for further use. UVcuring a single batch of monomer mixture yielded around 12-15 lenses.The same protocol was employed to synthesize silicone hydrogels from amonomer mixture batch comprising DMA (0.8 mL), TRIS (0.8 mL), DBE-U12(0.8 mL), EGDMA (0.1 mL), NVP (0.12 mL), and the photo-initiator,Darocur® TPO (12 mg).

2.3 Pigment Extraction

The organic food colorants considered in this study are solidparticulate powders at room temperature. The dissolution of food powdersin organic solvents was adopted as the principle extraction procedure(Refs. 29, 34, 41, 57, and 65). The color is due to the presence ofpigments that can be extracted in organic liquids such as ethanol.Powders were soaked in ethanol (6 mL) at loadings ranging from 0.5 wt. %to 33 wt. %, and in some cases up to 50% for an extraction time of 12hours, after which the pigmented solution was passed through a syringefilter to screen out the leached turmeric particles greater than 0.22 μmin size.

The yield, i.e., mass of pigment extracted per gram of powder wasdetermined by evaporating the solvent and measuring mass of pigment thatwas extracted from a given amount of powder. Specifically, food powders(2 g) were added to ethanol (6 mL) and mixed briefly for 2-3 minutes tofacilitate dissolution of extractable pigments. After an extraction timeof 12 hours, the organic solvent was passed through a 0.22 pm nylonsyringe filter to remove larger food colorant particles. The colloidaldispersion was kept in a ventilated enclosure to facilitate evaporationof ethanol at a room temperature of 25° C. Heating of the pigmentedethanol solution or retaining extracts in a temperature-controlled ovenwas not considered to avoid degradation of temperature sensitivepigments in spinach powder and paprika. The mass of the extractedpigment was measured after ethanol evaporation and used to determine theyield.

2.4 Absorption Spectra of Food Colorants

The potential of extracted pigments to selectively block a targetedwavelength range was characterized by measuring the absorbance spectraby UV-Vis spectrophotometry (Genesys™ 10 UV, Thermo Spectronic,Rochester, N.Y., USA) in the spectral range of 200-500 nm. Theabsorbance of extracted pigments is determined by its concentration inthe aqueous loading solution and molar absorptivity. The measured yieldfrom a 1:3 ratio of powder to ethanol was used to determine theconcentration of the extracted pigment in ethanol. Due to highabsorbance of the pigments, serial dilutions with ethanol were requiredto yield a calibration solution with a concentration of 0.053 mg/mL forturmeric, 0.426 mg/mL for spinach powder, 0.54 mg/mL for paprika and0.26 mg/mL for woad powder respectively. The Beer-Lambert's lawdescribing the relationship between absorbance of the food colorants andits corresponding concentration was used to compute the molarabsorptivity of the pigment,

A(λ) = ɛ(λ)Cl₀,

where l₀ is the path length (1 cm) and C is the concentration of thefood colorant in ethanol. Next, the absorbance of the solutions obtainedvia extraction at lower powder loadings (0.6 wt. %-17.4 wt. %) and molarabsorptivity obtained earlier was used to estimate the pigmentconcentration. Table 1 presents the amount of pigment extracted withincreasing food colorant loadings in ethanol. The relationship betweenfood colorant mass and the extracted pigment is linear for all foodcolorant types expect for pigments extracted from woad powder. Thespectra of pigments extracted from turmeric, spinach powder, paprika,and woad powder were in agreement with the spectra published in theliterature (Refs. 76-80).

TABLE 1 loading in 6 ml ethanol (g) Food Colorant 0.03 0.06 0.1 0.2 0.250.5 1 2 3 Type Extracted pigment (mg) Turmeric 1.68 5.34 5.51 11.4119.22 27.77 58.21 106.96 159.26 Paprika 2.59 5.57 10.43 23.98 33.8062.01 120.83 239.55 — Spinach powder 3.05 5.07 8.13 15.11 15.61 33.8160.47 121.19 220.95 Woad powder 0.11 0.18 0.29 0.42 0.44 0.60 0.76 0.87 1.05

2.5 Incorporation of Pigments into Hydrogel Lenses

A pre-polymerized p-HEMA or silicone hydrogel lens of 18 mm diameter and˜40 μL gel volume was introduced into a scintillation vial containingfood colorant/ethanol solution (6 mL). The concentration of the pigmentvaried from 0.006 wt. % -3.25 wt. % for turmeric, 0.054 wt. %-4.81 wt. %for paprika, 0.064 wt. %-4.45 wt. % for spinach powder and, 0.002 wt.%-0.022 wt. % for woad powder.

The soaked gel was left for 12 hours to ensure pigment equilibration atroom temperature (25° C.). The soaking of p-HEMA and silicone lenses inethanol causes the pores present in the hydrogel matrix to swellallowing the pigment to diffuse into the lens. The swollen pigmented gelwas finally removed from the solution using a tweezer and air-dried toenable shrinking of the porous hydrogel network. The dried hydrogel waslater rinsed with a quick ethanol dip to extract pigment depositsadsorbed on the surface of the lenses. The lenses were later rinsed inPBS to shrink the tinted lenses to their pre-deformed shape and storedin PBS medium (3 mL) for further experiments. FIGS. 2A-2C showrepresentative images of solutions containing pigments extracted byincorporation of 0.5 wt. %-33 wt. % of turmeric, paprika, spinach, woadpowder, and a 1:1 mixture of turmeric/spinach and turmeric/paprikapowders in ethanol and the corresponding images of tinted p-HEMA andsilicone hydrogel lenses.

2.6 Direct Pigment Entrapment through In Situ Polymerization

An in situ free radical polymerization approach was also employed toentrap the pigment and induce a stable tint. The HEMA or siliconemonomer mixture along with dispersed particles and the ethanol solublepigment extract was left for 12 hours prior polymerization. The samecomposition described in section 2.2 was used along with the addition of0.5-33 wt. % of turmeric, paprika, woad, and spinach powder to themonomer mixture.

2.7 Transmittance Measurements of Tinted p-HEMA and Silicone HydrogelLenses

The soft contact lens (p-HEMA/silicone hydrogel) were taken out of thePBS medium and blotted with a Kimwipe to remove residual solution on thesurface of the lens. The dried hydrogel was carefully mounted on theouter surface of the quartz cuvette by forceps without inducingstructural damage to the hydrogel material. The outer surface of thecuvette chosen for affixing the hydrogel was a region visible throughthe cell holder's aperture to allow exposure to a monochromatic UV beamfor recording the transmittance spectra. The transmittance measurementswere taken at a 1 nm interval in the spectral bandwidth of 190 nm-1100nm on UV-Vis spectrophotometer (GENESYS™ 10 UV, Thermo Spectronic,Rochester, N.Y., USA). The spectral bandwidth of 190 nm-1100 nm waschosen to gauge the UV-blocking capability of the lenses in the UVRrange from 190 nm-400 nm, HEV radiation or blue-light filtering abilityin the visible range from 385 nm-500 nm and, its ability to transmit therest of visible radiation in the range of 500 nm-700 nm. The percentageof UV radiation blocked by the tinted soft contact lenses in the UVRrange was quantified for three spectral subdivisions namely, UVC (190nm-280 nm), UVB (280 nm-315 nm) and, UVA (320 nm-400 nm). The measuredtransmittance was converted to absorbance:

${{A(\lambda)} = {{- \log_{10}}\frac{T(\lambda)}{100}}},$

which was then fitted to the Beer Lambert's law to obtain concentrationof the pigments in the lens. Data in the range where the pigments absorbstrongly was used in the fitting. The concentration of the food colorantin both the phases obtained through absorbance measurements were laterfit to a linear model:

C_(lens) = k C_(loading).

This theoretical model serves as a design tool for determining whatconcentration is needed in the loading solution to achieve the desiredconcentration in the lens. FIG. 5 shows representative plots indicatinga linear relationship between the pigment concentration in the hydrogelphase and that in the aqueous loading solution.

2.8 SEM Imaging of Tinted Hydrogel Lenses

To substantiate the presence of pigment-imparting particles phaseseparated in the hydrogel matrix, scanning electron microscopy (SEM)images of pigmented contact lenses were recorded. Dried hydrogel sampleswere placed on a carbon tape mounted on a silicon wafer. The images wereobtained on FEI Nova NanoSEM 430 in the Nanoscale Research Facility(NRF) at the University of Florida, Gainesville. Tinted p-HEMA andsilicone hydrogels were sputter coated with an ultra-thin, 10 nm thicklayer of electrically conducting gold-palladium alloy priorhigh-resolution SEM imaging. This pre-imaging procedure is done toprevent charging of hydrogel samples from accumulation of staticelectric fields. The synthesized hydrogel specimens were imaged at anaccelerating voltage of 10 kV and a magnification range of 2500× to120000×.

3. Results and Discussions 3.1. Molar Absorptivity and Food ColorantConcentration in Tinted Lenses

FIGS. 3A-D show representative data for the measured absorbance spectrafor all the pigmented lenses and the corresponding fits to Equation 1used to quantify the amount of pigment entrapped in the lens phase. FIG.3E summarizes the molar absorptivities of turmeric, paprika and spinachpowders. It was observed that paprika, spinach and woad powder are noteffective UV blockers due to low molar absorptivity values in the UVBand UVA range. Turmeric, on the other hand with two aborption peaks at239 and 412 nm respectively shows superior class 1 UV blockingcharacteristic features. This is further strongly evidenced by thetransmittance measurements of turmeric loaded p-HEMA and siliconehydrogel lenses with >97% UVA, UVB and high energy visible (HEV)raditions.

3.2. Transmittance Studies of Pigmented p-HEMA and Silicone HydrogelLenses

FIG. 5A shows the transmission spectra of turmeric pigment loaded p-HEMAlenses prepared by soaking a 200 μm thick pre-polymerized p-HEMAhydrogel lenses in filtered turmeric-ethanol loading solution (6 mL)with loadings of turmeric in ethanol ranging from 0.5 wt. %-33 wt. %.The resultant loadings of turmeric partitioned into the p-HEMA lenseswere estimated to be in the range of 17.09 μg-1 mg of turmeric loading/gof dry lens. The modified lens retained >90% transmittance from 570nm-750 nm which corresponds to a yellow-orange-red light band of thevisible range in the electromagnetic spectrum. The benefits of higherturmeric loadings to generate a darker hue without compromisingtransparency of the lenses were exploited by this approach of tinting apre-polymerized hydrogel. Further, a more compelling result is thepotential classification of these designed lenses as class 1 UV blockerswith retention of >90% transparency of visible light in theelectromagnetic spectrum. In addition to blocking >95% of the UVAspectrum, pigmented turmeric loaded p-HEMA lenses also provide anadditional benefit of filtering >90% of the high energy visibleradiation whose chronic exposure is harmful for the retina, thusimpacting the processing of physical objects by visual centers ininfants (Ref. 9). A lens diameter of 18-22 mm ensures complete pupillarycoverage which limits a peripheral glare or intensity shifts that couldpotentially trigger symptoms related to abnormal vision (Refs. 69-71).

A similar trend is seen for turmeric loaded silicone hydrogels (FIG. 6A)prepared by soaking control lenses in turmeric/ethanol solutions, whichpotentially screens out >97% of UVA-UVC spectrum with <10% loss oftransparency in the visible light spectrum. In a 2013 neurologicalresearch study, prolonged exposure to blue light evidenced initiation ofcortical spreading depression (CSD), an underlying cause for triggeringmigraine aura through propagation of neuron activity (Refs. 70-71). Theyellow-tinted lenses with its ability to phase out >97% HEV radiation iswell-suited to serve as ophthalmic devices for migraine preventivetherapy. In comparison to p-HEMA lenses, silicone hydrogels are moreeffective UV-blockers with >60% cumulative UV radiation screening forlower turmeric loading of 43.20 μg/g silicone in the hydrogels. Sincethe microstructure of silicone hydrogels contain co-continuousmorphology comprising of DMA and TRIS, the adsorbed hydrophobic turmericlikely partitions into the polymerized TRIS phase, thus forminglocalized turmeric-rich zones with high UV-blocking capacity. An 18%excess loading of turmeric in silicone hydrogels in comparison toturmeric loaded p-HEMA gels supports this hypothesis.

FIG. 6B shows transmittance data for silicone lenses tinted withdifferent loadings of spinach powder generating a green hue.Transmittance measurements were taken 24 hours after lens preparation.p-HEMA and silicone hydrogel lenses with >1 mg of spinach powder loadingexhibit class 1 UV blocking characteristics with >70% screening of HEVradiations. Silicone hydrogels loaded with 336.35 μg of spinach powdershow an average of 24% reduction in green-yellow light band withselective filtering of a longer-range bandwidth (near-red region). Suchexclusive features of the green-tinted lenses, along with their abilityto filter visible radiation from selective wavelength bandwidth, showtheir potential as optical devices designed for migraine therapy. Amajor limitation involved with spinach powder loaded lenses is thereduction in tint due to degradation of the extracted pigment after aweek's exposure of these lenses to sunlight. A green-tinted lens with a1 mg spinach powder/g dry lens loading shows an 82.46% degradation ofthe active pigment in these lenses (FIG. 6E). Another potential drawbackcaused by pigment degradation is the transmission of >20% UVA radiationwhich contravenes with the FDA guidelines requiring >95% filtering ofthe same. Table 2 summarizes the amount of active extract in the lensesloaded with spinach powder after a 7-day PBS storage. An 82.46%degradation in the spinach powder extract is observed.

TABLE 2 % Degradation in spinach powder green-tinted silicone hydrogellenses Food Colorant Loading in 6 ml ethanol/g 0.03 0.06 0.1 0.2 0.5 1Spinach mass in lenses 39.542 92.731 150.4 336.36 495 1038 afterpreparation/[μg/g] Spinach mass in 11.184 14.059 30.953 48.667 72.722125.16 degraded lenses/[μg/g] Volume of lens/(μL) 48.4 47.4 46.5 47.746.7 48 Spinach concentration/(μg/mL) 11.184 14.059 30.953 48.667 72.722125.16 % Degradation 71.717 84.84 79.42 85.531 85.309 87.943

To reduce degradation of the spinach pigment, turmeric was added to thespinach/ethanol solution to extract a combination of pigments from boththe food colorants. The motive behind turmeric's addition is its highstability under prolonged sunlight exposure and its effective HEVblocking capacity which can potentially retard the degradation ofspinach pigment extract. FIG. 6F shows the representative transmittancespectra of 200 μm thick turmeric/spinach powder loaded green-pigmentedsilicone hydrogel lens after exposure to sunlight for 7 days. Thetransmittance measurements of pigments extracted from a 1:1 mixture ofturmeric and spinach (2.4 wt. %-15 wt. %) in ethanol indicate a 50%reduction in degradation of spinach in these lenses. Other foodcolorants including woad powder and paprika were also used to render thelenses with a pink and orange hue respectively. Transmittancemeasurements shown in FIGS. 6C-6D indicate that these pigments promoteselective absorption of a narrow range of wavelengths (430-500 nm and490-625 nm), thereby reducing overlap between red-green and blue-yellowcolors. This aids in enhanced color perception and can serve as apotential optical device for people with Deutranopia. Tritanopia orblue-yellow color blindness is a rarer form of color-blindness occurringin ˜1% of the male and 0.03% of the female population. Siliconehydrogels tinted with paprika promotes a yellow-orange tint to thehydrogel, which can selectively filter portions of cyan and green light(˜450-510 nm), thus aiding CVD patients to discriminate between blue andyellow hues of the objects that are visually processed. A summary ofcommon eye disorders and tinted lenses synthesized for their effectivetreatment is presented in Table 3. The characteristic wavelength rangeblocked to achieve therapeutic effect is also summarized.

TABLE 3 Wavelength range Type of Indication Lens type filtered (nm)Therapeutic effect Retinal damage from Turmeric (T) 190-495 nm (T) Class1 UV Blockers UV exposure silicone/p-HEMA with >95% blocking of lensesthe UVR spectrum. Effective in preventing retinal damage. Migraine/Spinach (S), 190-450 nm & UV Blockers with >70% Photophobia Paprika (P),620-650 nm (S), blocking of UVR Turmeric/spinach 190-495 nm & spectrumand >20% (T/S), and 620-650 nm (T/S), blocking of visibleTurmeric/Paprika 190-550 nm (P), spectra aiding in (T/P) silicone190-490 nm (T/P) reduction of light lenses intensity. Effective inreducing the frequency of attacks among migraineurs. Amblyopia Spinach(S), 190-450 nm and UV blockers with >70% Paprika (P) and 620-650 nm(S), blocking of UVR Turmeric (T) 190-550 nm (P), spectrum minimizessilicone lenses 190-495 nm (T) retinal damage, critical among the aginginfant population. Effective occlusion patches and refractive errorcorrection lenses. Lens pair with different tints effective forcorrecting the amblyopic eye through forced focus on specific images.Color Vision Paprika (P) 473-622 nm (W) and Selective filtering ofDeficiency (CVD) and Woad (W) 450-520 nm (P) aiding enhanced colorsilicone lenses perception among CVD patients.

FIG. 5B shows the transmission spectra of tinted p-HEMA hydrogel lensesdesigned through direct incorporation of different turmeric loadings inHEMA/water monomer mixture (FIG. 5C) prior polymerization. Transmissionspectra of 200 μm thick p-HEMA tinted lenses with 6.54-18.95 μg ofturmeric loading/g of dry lens exhibit potential for a class 2UV-blocking lenses with additional HEV radiation filtering, but fallsshort of FDA guidelines due to >20% transmission of UVB radiation.Higher turmeric loadings >65 μg of turmeric loading/g of dry lensresolve the issue with >95% UV radiation filtering but, affects thetransmission of visible light and transparency of the fabricated lenses.The loss of transparency in the lenses for higher turmeric loadingscould potentially be attributed to the phase separation of extractedpigment during free radical polymerization of HEMA. The phase separatedpigment form particles leading to aggregation. To overcome aggregationof particles within the monomer mixture in the mold duringpolymerization, the mass of photo initiator, Darocur TPO was increasedto enhance the rate of polymerization. It was observed that the timescale for aggregation was faster in comparison to the rate ofpolymerization of the hydrogel phase even when the concentration of theinitiator was increased to 1 wt. %. The addition of the photo initiatormore than 1 wt. % resulted in a turbid HEMA monomer mixture whichresulted in translucent hydrogels. A loss of >50% transmission ofvisible light for higher turmeric loadings makes it a less attractiveroute to fabricate UV-blocking lenses and was not further employed forrest of the food colorants.

3.3. Pigmented Commercial and Scleral Lenses

The size and shape of fabricated tinted lenses could potentially betailored for synthesizing scleral lens for patients suffering fromconditions like Keratoconus, an irregular corneal surface. FIG. 7B showslab-made scleral lenses placed on the surface of a control Albino rabbitcadaver eye (FIG. 7A). The scleral lenses were synthesized bypolymerizing silicone monomers described in section 2.2 in ACUVUE®OASYS® commercial blister packs to induce curvature. Tinted sclerallenses of 18-20 mm diameter ensures complete pupillary coverage, thuslimiting a peripheral glare or intensity shifts that could potentiallytrigger symptoms related to photophobia. The fabricated scleral lensespresented in the figures were tinted with extracted pigments fromturmeric and spinach powders. FIG. 7C demonstrates the induction of tintto commercial lens brands including ACUVUE® TruEye® and Air Optix™ NIGHT& DAY™ AQUA. Transparent tinted lens synthesized with ACUVUE® TruEye®and Air Optix™ NIGHT & DAY™ AQUA show promise of effective and efficientintegration of the pigment in commercial lenses.

3.4. Pigment Leaching and Effect of Lens Sterilization on UV Blocking

Organic food colorants used in this study namely turmeric and woadpowder are known for their medicinal properties. Bio-active componentsin turmeric possess anti-inflammatory, anti-cancer and anti-microbialproperties. Curcumin, a principal pigment in turmeric is linked toimproved brain function (BDNF booster), effective rheumatoid arthritisand blood pressure management. Though no studies reveal or raise thecytotoxicity concerns of turmeric diffusion into the tear film,preventing pigment leaching from these biocompatible devices is usuallypreferred to minimize the potential for toxicity. The potential forrelease of the pigment was measured from turmeric-tinted lenses bystoring the lenses in PBS medium (3 mL) for 7 days. Before storing thelenses in PBS, the tinted lenses were rinsed in ethanol for ˜10 s toremove the surface adsorbed turmeric deposits. These silicone lenseswere air-dried and immersed in PBS medium (3 mL) to monitor leaching ofturmeric pigment embedded within the hydrogel matrix as shown in FIG.5D. FIG. 5E presents the UV spectra of turmeric pigment leached from thesurface of the tinted lenses after 7 days of PBS storage. The releasedata indicates negligible pigment diffusion in the measured UV range,indicating that most of the pigment in entrapped within the hydrogelmatrix. The transmittance of the turmeric and woad powder loaded lenseswere measured again to examine >95% retention of UV blockingcharacteristics after pigment leaching in the PBS medium. The effect ofsterilization of the contact lens on stability of the pigment was alsoexamined. The yellow-tinted lenses stored in a 3 mL PBS medium weresterilized by placing them in an oven pre-heated to 100° C. for 3 hrs.The transmittance data shown in FIG. 5F for both turmeric loaded lensesand turmeric/paprika loaded lenses show negligible change indicatingpreservation of UV-blocking characteristics and a stable tint.

3.5. SEM Images of Pigmented Silicone Hydrogels

The pigmented hydrogel matrices were imaged by SEM to inspect thepresence of precipitated pigment particles in the polymer matrix. Thepigmented silicone hydrogels samples imaged by SEM were synthesized bysoaking the control lenses in 17.42 wt. % turmeric/ethanol, spinachpowder/ethanol, and paprika/ethanol powder solutions respectively. SEMimage of turmeric loaded silicone lens (FIG. 8A) does not revealpresence of particles in the hydrogel matrix at 40000× magnificationfactor. Investigation of a different cross-sectional area in thehydrogel matrix revealed presence of non-spherical particles at amagnification factor of 60000-120000× (FIGS. 8B-8D). The particle sizecharacterization done in ImageJ software revealed a Feret diameter of 50nm with a 1:1 aspect ratio. Though, the geometric properties of theseparticles does not impact extended drug delivery, potential binding ofcertain drugs to these hydrophobic particles may find applications incontrolled delivery. The dimensions of the largest bound particleanalyzed at 120000× in the silicone hydrogels is less than 86 nm, whichwill still not scatter significant light while the smallest sizes aretoo large to diffuse out of the lenses. Similarly, SEM imagesrespresented in FIGS. 8E-8F taken at 120000× correspond to lenses tintedwith spinach and paprika powders show presence of particles in the lensmatrix.

The pigment from the agro products considered here was extracted intoethanol. The ethanol soluble pigment is ideal for incorporation intocontact lenses to produce tinted lenses. The swelling of the p-HEMA andsilicone lens in ethanol allows direct entrapment of the pigment in thehydrogel phase. The pigments are larger than the pores in the hydrogelwhich allow effective retention with negligible leaching. A 400 μg-1 mgturmeric loaded p-HEMA and silicone hydrogels act as class 1 UV blockerswith retention of >90% transparency of visible light in theelectromagnetic spectrum. In addition to blocking >95% of the UVAspectrum, pigmented turmeric loaded p-HEMA lenses also provide anadditional benefit of filtering >90% of the high energy visibleradiation whose chronic exposure is harmful for the retina. Spinach,paprika and woad powder loaded silicone lenses impart different shadesmitigating >20% visible light transmission from selective wavelengths.They can potentially be used for treating photophobia, a symptom ofsevere migraine attacks, managing color deficient vision. Siliconelenses with loadings >1 mg/g food colorant also find practical use inAmblyopia therapy.

Table 4 below summarizes food colorant composition and extractioninformation, along with associated references.

TABLE 4 Food Extraction Colorant Color^(#) Composition References*Technique References** Turmeric Yellow Curcumoids Refs. 29, 31, SoxhletRefs. 29, 32, Curcumoid composition 32, 34, 35, extraction of 34, 39,and 76 42-60% Curcumin and 39 ground 24-30% turmeric in Demethoxyorganic curcumin solvents 10-34% Bisdemethoxy curcumin Paprika OrangeCarotenoids Refs. 40-54 Dissolution of Refs. 41, 43- Carotenoidcomposition ground paprika 50, 78, and 80 10-26.8% β- powder in Caroteneorganic 24.2% solvents Xanthophylls and isomers 49% Xanthophyll estersSpinach Green Chlorophyll-a and Refs. 57-62 Dissolution of Refs. 57-62powder Chlorophyll-b ground and 77-78 spinach powder in organic solventsWoad Pink Indigorubin Refs. 63 and Soxhlet Refs. 65-66 powder 65-68extraction of and 79 powdered Isatis tinctoria leaves in organicsolvents ^(#)Color imparted to the lens. *References pertaining tocharacterization of pigment composition. **References pertaining topigment spectral information.

It should be emphasized that the above-described embodiments of thepresent disclosure are merely possible examples of implementations setforth for a clear understanding of the principles of the disclosure.Many variations and modifications may be made to the above-describedembodiment(s) without departing substantially from the spirit andprinciples of the disclosure. All such modifications and variations areintended to be included herein within the scope of this disclosure andprotected by the following claims.

What is claimed is:
 1. A contact lens comprising a one or morecolorants, wherein the colorants comprises two or more of: turmeric,paprika, spinach, woad, or carbon black.
 2. The contact lens of claim 1,wherein the colorant comprises two or more of: turmeric, paprika,spinach, or woad.
 3. The contact lens of claim 1, wherein the colorantcomprises three or more of: turmeric, paprika, spinach, or woad.
 4. Thecontact lens of claim 1, wherein the amount of turmeric, when present,in the hydrogel is about 2 mg/g hydrogel to 700 micrograms/g hydrogel orthe amount of spinach, when present, in the hydrogel is about 30 mg/ghydrogel to 600 micrograms/g hydrogel or the amount of paprika, whenpresent, in the hydrogel is about 15 micrograms/g hydrogel to 300micrograms/g hydrogel or the amount of woad, when present, in thehydrogel is about 15 micrograms/g hydrogel to 80 micrograms/g hydrogel.5. The contact lens of claim 1, further comprising a hydrogel, whereinthe hydrogel entraps the colorants within the hydrogel or the colorantsare absorbed onto a surface layer of the contact lens.
 6. The contactlens of claim 1, further comprising a hydrophilic ophthalmic drug, ahydrophobic ophthalmic drug, vitamin E, or a combination thereof.
 7. Acontact lens comprising a one or more colorants, wherein the colorantscomprises one or more of: turmeric, paprika, spinach, or woad, whereinthe amount of turmeric, when present, in the hydrogel is about 2 mg/ghydrogel to 700 micrograms/g hydrogel or the amount of spinach, whenpresent, in the hydrogel is about 30 mg/g hydrogel to 600 micrograms/ghydrogel or the amount of paprika, when present, in the hydrogel isabout 15 micrograms/g hydrogel to 300 micrograms/g hydrogel or theamount of woad, when present, in the hydrogel is about 15 micrograms/ghydrogel to 80 micrograms/g hydrogel.
 8. The contact lens of claim 7,wherein the colorant is turmeric, wherein the amount of turmeric in thehydrogel is about 2 mg/g hydrogel to 700 micrograms/g hydrogel.
 9. Thecontact lens of claim 7, wherein the colorant is paprika, wherein theamount of paprika in the hydrogel is about 15 micrograms/g hydrogel to300 micrograms/g hydrogel.
 10. The contact lens of claim 7, wherein thecolorant is spinach, wherein the amount of spinach in the hydrogel isabout 30 mg/g hydrogel to 600 micrograms/g hydrogel.
 11. The contactlens of claim 7, wherein the colorant comprises two or more of:turmeric, paprika, spinach, or woad.
 12. The contact lens of claim 7,wherein the colorant comprises three or more of: turmeric, paprika,spinach, or woad.
 13. The contact lens of claim 7, wherein the colorantconsists of one or more of: turmeric, paprika, or spinach.
 14. Thecontact lens of claim 7, wherein the colorant consists of two or moreof: turmeric, paprika, spinach, or woad.
 15. The contact lens of claim7, wherein the colorant consists of three or more of: turmeric, paprika,spinach, or woad.
 16. The contact lens of claim 7, further comprising ahydrogel, wherein the hydrogel entraps the colorants within the hydrogelor the colorants are absorbed onto a surface layer of the contact lens.17. The contact lens of claim 7, further comprising a hydrophilicophthalmic drug, a hydrophobic ophthalmic drug, vitamin E, or acombination thereof.
 18. The contact lens of claim 7, further comprisingvitamin E, wherein the vitamin E loading is 5% to 40% (w/w) in thecontact lens.